Manipulations will be studied that (1) modify the processing of sensory input in the spinal cord dorsal horn, and (2) are accompanied by pronounced abnormalities of somatosensory perception in animals and humans. The goals are to detect and quantitatively characterize the effects of each manipulation on the differential responses of normal contralateral SI cortex to precisely controlled mechanical vs. thermal stimulation of the skin. Anesthetized squirrel monkeys will serve as subjects. The methods of near-infrared optical intrinsic signal (OIS) imaging and extracellular microelectrode recording of spike discharge activity will be used to characterize (both before and after each manipulation) the SI responses to thermal and mechanical stimulation of the skin at both the neuron population and single neuron levels of analysis. The project is expected to (1) reveal a hitherto unappreciated sensitivity of the SI cortical response evoked by natural skin stimuli to manipulations that modify the processing of sensory input by spinal cord dorsal horn neurons; and (2) establish the extent to which the altered SI response to natural skin stimuli can be attenuated/reversed by selective ablation of NK-1 (Substance P) receptor expressing neurons in the superficial dorsal horn of the spinal cord, or by the selective block of spinal cord NMDA receptors.